Phenylalkylamine stimulants,
hallucinogens, and designer drugs

Glennon RA
Department of Medicinal Chemistry,
School of Pharmacy,
Medical College of Virginia,
Virginia Commonwealth University,
Richmond 23298-0581.
NIDA Res Monogr 1991; 105:154-60


Phenylalkylamine derivatives produce several types of behavioral effects including central stimulation and hallucinogenic activity. SAR are being formulated and already (a) it has been demonstrated that each of these types of activities is associated with a distinct SAR, and (b) it is now possible to use these SAR to make predictions as to whether the stimulus effects of certain PAAs are primarily AMPH-like or DOM-like. The AMPH-like nature of PAAs seems to involve a dopaminergic mechanism whereas DOM-like activity involves a serotonergic (in particular a 5-HT2) mechanism. It is apparent, however, that there is an additional type of activity emerging from studies with some PAAs that is neither solely AMPH-like nor DOM-like. MDA seems to produce both types of actions and may even produce this third type of effect. MDMA produces AMPH-like and MDA-like effects, but does not produce DOM-like effects. Other agents, such as MDE and PMMA, produce neither AMPH-like nor DOM-like effects but clearly produce MDMA-like stimulus effects. Thus, there is a third type of SAR that may be formulated. In all likelihood, however, few PAAs will be shown to produce a single "pure" activity and because there are some similarities in the different SARs (even though there are some very clear differences) it is not unreasonable to assume that many PAAs will produce more than one type of effect or will display vestiges of one or more different components of action. Therefore, although a PAA may be classified as primarily producing one type of effect, it should be understood that the other types of effects are not necessarily absent.

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